The final goal of our work is to eliminate the ill-effects of alcohol consumption, which is one of mankind's major problems. The possibility of approaching this goal rests upon a clear understanding of the alcohol combustion and an increased knowledge of the ill-effects of the alcohol itself and its first oxidation product, acetaldehyde, and the processes involved in or disturbed by its combustion. We intend to continue our work on the enzyme performing the first step in the oxidation of alcohol, liver alcohol dehydrogenase. Particular attention will be given to the human enzyme which consists of a family of closely related isoenzymes with varying effects on ethanol and other alcohols, e.g. hydroxysteroids and hydroxy fatty acids. We intend to continue our studies on the kinetics and mechanism of the isolated isoenzymes. These studies involve the application of synthetic inhibitors, where extensive synthetic work has shown pyrazole derivatives to be the most effective inhibitors of liver alcohol dehydrogenase. The synthetic work on new inhibitors will continue with a twofold purpose: 1. comparing the effect of a large number of inhibitors on the human enzymes with the corresponding effect on the horse liver alcohol dehydrogenase, where the three-dimensional structure is known, we can get increased knowledge of the structure of the substrate pocket of the enzyme. This will be a guide in the further synthetic work. 2. a strong and nontoxic inhibitor would allow very interesting animal experiments to study the ill-effects of alcohol versus acetaldehyde by inhibiting the aldehyde production caused by liver alcohol dehydrogenase.